The incidence rate of thrombotic diseases, such as stroke/infarction, ranks first in a variety of diseases. There is an increasing trend in the incidence rate of the diseases in recent years, and the diseases become a serious threat to human health. Drug treatment of the thrombotic diseases is the focus and hotspot of treating thrombosis. Currently, there are many limitations on clinically applied thrombotic drugs, and searching for a safe and effective new thrombus drug is one of the research hotspots.
According to present research, in addition to anti-platelet aggregation and anti-thrombotic activities, 3S-1,1-dimethyl-6,7-dihydroxy-1,2,3,4-tetrahydro isoquinoline-3-carboxylic acid also has free radical scavenging activity. Moreover, in Chinese Patent Publication CN101497651B, filed Jan. 30, 2008, 10 tetrahydroisoquinoline compounds having thrombolytic activity were disclosed. These tetrahydroisoquinoline compounds include 3S-6,7-1,2,3,4-tetrahydro-6,7-dihydroxy-isoquinoline-3-acyl-Pro-Ala-Lys, 3S-6,7-1,2,3,4-tetrahydro-6,7-dihydroxy-isoquinoline-3-acyl-Arg-Pro-Ala-Lys, 3S-6,7-1,2,3,4-tetrahydro-6,7-dihydroxy-isoquinoline-3-acyl-Ala-Arg-Pro-Ala-Lys, 3S-6,7-1,2,3,4-tetrahydro-6,7-dihydroxy-isoquinoline-3-acyl-Gly-Arg-Pro-Ala-Lys, 3S-6,7-1,2,3,4-tetrahydro-6,7-dihydroxy-isoquinoline-3-acyl-Gln-Arg-Pro-Ala-Lys, 3S-2-[Pro-Ala-Lys]-1,2,3,4-tetrahydro-6,7-dihydroxy-isoquinoline-3-carboxylic acid, 3S-2-[Arg-Pro-Ala-Lys]-1,2,3,4-tetrahydro-6,7-dihydroxy-isoquinoline-3-carboxylic acid, 3S-2-[Ala-Arg-Pro-Ala-Lys]-1,2,3,4-tetrahydro-6,7-dihydroxy-isoquinoline-3-carboxylic acid, 3S-2-[Gly-Arg-Pro-Ala-Lys]-1,2,3,4-tetrahydro-6,7-dihydroxy-isoquinoline-3-carboxylic acid, and 3S-2-[Gln-Arg-Pro-Ala-Lys]-1,2,3,4-tetrahydro-6,7-dihydroxy-isoquinoline-3-carboxylic acid. The compounds above were abbreviated as “6,7-dihydroxy-isoquinolines having thrombolytic activity.” However, the effective dosages of these 6,7-dihydroxy-isoquinolines having thrombolytic activity are higher, and the anti-thrombotic activity and the free radical scavenging activity were not disclosed or verified. Furthermore, the efficacy in treating stroke was demonstrated to be effective only at the time of stroke onset. As for treating stroke beyond 30 minutes from onset of syndrome, the efficacy was not disclosed or verified.
Therefore, for effectively and safely treating thrombotic diseases in clinical practice, a novel compound that simultaneously has thrombolytic, anti-thrombotic, and free radical scavenging activities, may effectively cross the blood-brain barrier (BBB), and may achieve the described effects at a low dose is needed.